Human neonates are predisposed to an increased risk of mortality from infection due to fundamental differences in the framework of innate and adaptive immune responses relative to those in the adult population. As one key difference in neonates, an increase in the immunosuppressive cytokine, IL-27, is responsible for poor outcomes in a murine neonatal model of bacterial sepsis. In our model, the absence of IL-27 signaling during infection is associated with improved maintenance of body mass, increased bacterial clearance with reduced systemic inflammation, and decreased mortality rates that correlate to preservation of glucose homeostasis and insulin production. To further elucidate the mechanisms associated with IL-27 signaling and metabolic fitness, we analyzed global transcriptomes from spleen, liver, pancreas, and hindlimb muscle during